This is a continuation of studies on epithelioid cell granuloma using experimental models induced by metals and other substances in man and animals. It is designed to examine granulomatous hypersensitivity in classical immunological terms and to understand biological factors determining sensitization, formation of epithelioid cells and organization of granulomas. The results are expected to provide insight into the pathogenesis of diseases such as tuberculosis and leprosy. Attempts will be made to induce typical organized epithelioid cell granulomas in laboratory animals and to transform mononuclear cells into epithelioid cells in vitro. Comparative chemical characterization of mononuclear cells and epithelioid cells will be achieved by biochemical techniques. Antibodies directed toward a unique protein from epithelioid cells will be used to study epithelioid cells immunohistochemically as well as to provide a diagnostic aid for granulomatous diseases.